The SAPHO syndrome in diffuse sclerosing osteomyelitis of the mandible: an oral and maxillofacial surgery perspective.

Chronic nonbacterial osteomyelitis (CNO) and SAPHO (syndrome of synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome are rare autoinflammatory diseases characterized by inflammatory manifestations of the skeletal system often accompanied by skin and less frequently intestinal and pulmonary involvement. Despite familial clustering being observed, the prevailing genetic causes are yet to be fully understood. This review article summarizes the current evidence on the genetic background of CNO. Rare functional variants in LPIN2, IL1RN, and FBLIM1 have been described in isolated individuals, suggesting monogenic inheritance, while more common susceptibility factors such as the HLA-B*27 allele and P2RX7 variants indicate amore complex mode of inheritance. Genetic overlaps with familial Mediterranean fever in the Turkish population and partial response of these CNO patients to colchicine could indicate ashared pathogenetic spectrum. In conclusion, the genetic architecture of CNO appears heterogeneous, encompassing susceptibility factors and, pathogenic variants with potential therapeutic implications. Lack of many solved cases underlines the necessity to perform further genetic research.

Successful Treatment of Comorbid SAPHO Syndrome and Hidradenitis Suppurativa with Upadacitinib.

Melanosis Coli Associated with SAPHO Syndrome: A Rare Coexistence Suggesting a Possible Gut–Bone Axis Link

Objectives: The purpose of this study is to identify clinical subtypes of SAPHO syndrome using cluster analysis, and to systematically investigate the associated clinical characteristics, therapeutic approaches, and short-term prognostic outcomes in order to enhance patient management. Methods: We recruited patients who had been diagnosed with SAPHO syndrome at Beijing Jishuitan Hospital. Bone lesions were assessed using a 99Tc bone scan. Based on bone lesions and clinical features, patients were categorized using a hierarchical clustering algorithm. Laboratory test results and prognostic differences were compared among clusters. Results: Overall, 135 patients were included. Cluster analysis identified three distinct clusters. Eighty-seven patients were assigned to cluster 1, characterized by anterior chest wall involvement; 74.7% also had skin involvement. Nineteen patients were assigned to cluster 2, characterized by spinal involvement, and 10.5% showed skin manifestations. Twenty-nine patients were assigned to cluster 3, characterized by peripheral bone involvement, with 24.1% exhibiting skin manifestations. Patients in cluster 3 were younger at disease onset (36.92 ± 16.62 years); their BASDAI and BASFI scores were lower (2.51 ± 1.18 and 0.89 ± 1.37, respectively). In cluster 1, significant reductions in Visual Analog Scale scores were observed at 1 and 6 months after treatment compared with baseline (7.08 vs. 2.59, p < 0.001, n = 63; 7.09 vs. 1.93, p < 0.001, n = 45). Similar improvements were noted in clusters 2 and 3 (7.18 vs. 3.00, p < 0.001, n = 11; 7.00 vs. 3.00, p < 0.001, n = 7; 6.70 vs. 2.65, p < 0.001, n = 20; 6.60 vs. 2.47, p < 0.001, n = 15). Conclusions: SAPHO syndrome may be classified into three subtypes: typical, axial, and peripheral. All subtypes show rapid improvement with timely treatment. Defining the clinical characteristics of these three subtypes can aid diagnosis and provide pathogenesis insights regarding this heterogeneous syndrome.

To investigate the practices of doctors in the diagnosis and treatment of adult SAPHO syndrome. A cross-sectional study was conducted by distributing online questionnaires to physicians across five hospitals, specifically targeting departments involved in the diagnosis and treatment of adult SAPHO syndrome, including rheumatology, dermatology, and orthopedics. A total of 103 clinical physicians participated in the survey.The three most commonly observed clinical features of adult SAPHO syndrome were elevated ESR and CRP (82/84), focal swelling and fever (73/84), and new lesions found on imaging (70/84). The primary diagnostic tools utilized were Whole body bone imaging (76.2%) and CT scans (60.1%), with less frequent use of MRI (22.6%) and positron emission tomography-computed tomography (PET-CT) (9.6%). Notably, only 14% of physicians reported never performing disease activity monitoring. Nearly all respondents (98%) selected nonsteroidal anti-inflammatory drugs (NSAIDs) as the first-line treatment. Additionally, 81% of physicians opted for target synthetic disease-modifying antirheumatic drugs (tsDMARDs), 78.6% for steroids, 71.4% for biological disease-modifying antirheumatic drugs (bDMARDs), 66.7% for conventional synthetic disease-modifying antirheumatic drugs (csDMARDs, and only 18.5% chose bisphosphonates (pamidronate and zoledronate). While Whole body bone imaging and CT scans are widely used for the early diagnosis of adult SAPHO syndrome, there is a gap in the utilization of MRI and the practice of disease activity monitoring. Physicians prefer commonly used rheumatic drugs, but there remains limited application of bisphosphonates. Highlight • Our study first systematically investigated Chinese physicians' perspectives on the diagnosis and treatment of adult SAPHO syndrome. • We pointed out that the utilization of imaging tools (such as MRI) and bisphosphonates was low, suggesting that the diagnostic strategy needs to be optimized. • This study may aid the research of SAPHO syndrome at home and abroad, providing references.

Targeted Therapy Outcomes in SAPHO Syndrome: A Systematic Review.

SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a rare autoinflammatory disorder characterized by diverse skeletal and dermatologic manifestations. Bone scintigraphy plays a pivotal role in diagnosis, with the classic "bullhead" sign reflecting anterior chest wall involvement. Nevertheless, atypical scintigraphic patterns, particularly spinal involvement, can pose diagnostic challenges. We report 2 cases: one demonstrating typical tracer uptake in the manubrium and bilateral sternoclavicular joints, and another exhibiting predominant spinal osteitis. These cases illustrate the broad spectrum of scintigraphic presentations in SAPHO syndrome and underscore the complementary utility of SPECT/CT in delineating atypical lesions and facilitating accurate diagnosis.

Clinical Images: Successfully treated mandibular osteomyelitis by tumor necrosis factor inhibitor in SAPHO syndrome.

Rapid remission of SAPHO syndrome with secukinumab

Monofocal and multifocal bone lesions in children and adolescents may result from various diseases. Apart from inflammatory entities malignancy is the most important issue to be ruled out. Various diseases. Apart from inflammatory origin malignancy is the most important issue to be ruled out. Imaging in particular magnetic resonance imaging (MRI) has an important role for the diagnostic process. Osteomyelitis and septic arthritis on the one hand and nonbacterial osteomyelitis and synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome (SAPHO) syndrome on the other may present with unspecific clinical symptoms and overlapping disease courses. Radiology is important not only for diagnostics but for treatment planning. This review focusses on questions to the radiologist from the clinician's view.

BackgroundSynovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is a rare disease which seems to have a multifactorial origin with genetic, environmental, immunologic, and infectious components.[1] Hidradenitis suppurativa (HS) is a chronic autoinflammatory keratinization disease that affects sweat glands.[2] Both SAPHO syndrome and HS are chronic, relapsing diseases that pose a severe impairment to a patient’s quality of life. While the coexistence of these 2 conditions is rare, this case presents a 28-year-old male with a co-presentation of SAPHO syndrome and HS.CaseA 28-year-old male from an Indian Ocean’s Island with a two-year history of multiple skin lesions including acne, pustules, and anorectal abscess and a 4-month history of recurrent musculoskeletal pain, presented to hospital with fever and an acute pain in the left elbow and in the right wrist increasing in recent days (Table 1). During examination, 2 synovitis were found and 10 cm by 10 cm ulcerations were observed in the axillary regions with serous discharge, granulation and sinus tracts which were later found to be HS. Anamnesis revealed that these skin lesions had been evolving for 2 years, and that the patient was reluctant to seek medical assessment. During hospitalization, blood work revealed leukocytosis, thrombocytosis, eosinophilia, and c-reactive protein reaching 137 mg/L. A bone scan revealed bilateral uptake on acromioclavicular and sternoclavicular bones and the first costochondral junctions, which was consistent with the diagnosis of SAPHO syndrome. After an infusion of pamidronate 60 mg, bone pain was considerably improved, and skin lesions abated with local care only.Table 1-Characteristics of patients with an association of SAPHO syndrome and hidradenitis suppurativa (HS)ConclusionAlthough the association of SAPHO syndrome and HS is unclear, this case demonstrates a rare example of the coexistence of these 2 diseases. This case supports previous literature which showed that HS in SAPHO syndrome was more common among African descents compared to other ethnicities.[2,3] It is crucial to look for signs of HS during physical examinations when there is a suspicion of SAPHO syndrome, as the co-presentation of these 2 conditions is often associated with poor response to medical therapy and more comorbidities.[2,3] Patients with HS may be hesitant to seek medical attention or reveal their skin lesions due to discomfort or embarrassment, leading to a progression of the disease. Identifying HS early during physical examination can help clinicians provide timely intervention and potentially preventing further complications, particularly in the more prevalent subgroup of African descents with HS and SAPHO syndrome. [1.] Girschick H. SAPHO syndrome [Internet]. Orphanet; 2019. Available from:https://www.orpha.net/en/disease/detail/793[2.] Crowley EL. SAGE Open Med Case Rep 2018;6:2050313X18778723. [3.] Steinhoff J. Journal of Clinical Rheumatology 2002;8:13-22.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare disease that is characterized by autoinflammatory lesions on both bones and skin. The diverse manifestations and limited understanding of its etiology have hindered the diagnosis and treatment of this condition. SAPHO syndrome is also classified as a primary inflammatory osteitis. The onset of osteoarticular involvement in this disease is typically gradual, and the identification of associated biomarkers may be crucial for accurate diagnosis, effective treatment, and a better understanding of its underlying mechanisms. We enrolled a total of 6 SAPHO patients and 3 healthy volunteers for this study. The miRNA expression profile in circulating exosomes was analyzed using next-generation sequencing. A total of 45 miRNAs were found to be differentially expressed in SAPHO patients. Linear discriminant analysis effect size analysis and Wilcoxon rank-sum test were employed to identify biomarkers based on these differentially expressed miRNAs. Among them, we selected 4 miRNAs as biomarkers for SAPHO syndrome, resulting in an area under the receiver operating characteristic curve of 1. The differentially expressed miRNAs indicated enrichment in immune system and endocrine system-related KEGG pathways, as well as infectious diseases and cancers. Furthermore, the most significantly enriched molecular functions in GO analysis were protein binding and catalytic activity. The exosomal miRNA profile in SAPHO syndrome exhibited significant changes, suggesting its potential as a candidate biomarker for diagnostic assistance, although further investigation is warranted to elucidate their role in the pathology.

Abstract Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) syndrome is a rare autoinflammatory disorder characterized by osteoarticular and cutaneous involvement. The anterior chest wall and axial skeleton are most frequently affected. Diagnosis relies on clinical presentation and characteristic imaging findings. We report the case of a 45-year-old woman presenting with anterior chest pain, inflammatory back pain, and palmar pustulosis. Imaging revealed clavicular hyperostosis and axial skeletal lesions compatible with SAPHO syndrome. Bone scintigraphy demonstrated the classic “bull’s head sign.” Initial treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) was insufficient, leading to the administration of intravenous zoledronic acid, which resulted in rapid and sustained clinical and biological remission. This case highlights the utility of multimodal imaging in the diagnosis of SAPHO syndrome and supports the efficacy of bisphosphonates as a therapeutic option in patients with suboptimal response to NSAIDs.

Painful scalp nodules in SAPHO syndrome.

Radiological diagnosis of SAPHO syndrome- A case report

Objective: To explore bone mass changes in patients with SAPHO syndrome, utilizing bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) and vertebral bone quality (VBQ) scores measured by MRI. Methods: Thirty-six patients with SAPHO syndrome at Peking Union Medical College Hospital from February 2014 to February 2024 were retrospectively collected with 36 age- and gender-matched healthy controls. DXA assessed BMD, corresponding T-score and Z-score of the lumbar spine (LS), femoral neck (FN), total hip (TH), and trabecular bone score (TBS). LS MRI T1-weighted imaging (T1WI) measured the VBQ scores. Correlations between BMD, TBS, and VBQ scores were analyzed using Pearson correlation. The predictive efficacy of VBQ scores for low bone mass and impaired bone microarchitecture in patients with SAPHO syndrome was assessed using receiver operating characteristic (ROC) curves, with the area under the curve (AUC), optimal diagnostic cut-off values, sensitivity, and specificity documented. Results: The mean age of patients with SAPHO syndrome was (44.8±9.5) years, with 8 (22.2%) males. There were 36 subjects in the control group with a mean age of (44.8±9.5) years and 8(22.2%) males. Compared to the controls, the case group had lower FN BMD, TH BMD, corresponding T-score and Z-score, TBS, and higher VBQ scores (all P<0.05). Compared to the controls, female patients in the case group had lower LS BMD, FN BMD, TH BMD, corresponding T-score and Z-score, TBS, and higher VBQ scores (all P<0.05), whereas only male patients in the case group had higher VBQ scores (P=0.028). Ten cases (27.8%) in the case group had low bone mass and 19 cases (52.8%) had impaired bone microarchitecture, higher than the 3 cases (8.3%) and 9 cases (25.0%) in controls respectively (both P<0.05). VBQ scores in the case group were negatively correlated with FN BMD, FN T-score, TH BMD, TH T-score, and TBS (r=-0.375, -0.391, -0.368, -0.361, and -0.389, respectively, all P<0.05). The AUCs of VBQ scores for predicting ROC curves of low bone mass and impaired bone microarchitecture in patients with SAPHO syndrome were 0.796 (95%CI: 0.649-0.944) and 0.694 (95%CI: 0.521-0.866), with a sensitivity of 100.0% and 47.4%, and a specificity of 53.9% and 88.2%, respectively. Conclusions: Patients with SAPHO syndrome present with low bone mass and impaired bone microarchitecture. VBQ score has a high sensitivity for predicting low bone mass and a high specificity for predicting impaired bone microarchitectural in patients with SAPHO syndrome.

Background: Juvenile spondyloarthritis (JSpA) is a heterogeneous group of diseases. An international consensus group developed the axial juvenile SpA (AxJSpA) classification criteria for this purpose, defining a homogeneous group of patients diagnosed with jSpA and experiencing axial symptoms before the age of 18 years. Aim: To validate this new set of criteria in our pediatric SpA patients. Methods: This study was held in the Hacettepe University Department of Pediatric Rheumatology. Juvenile SpA patients suspected of axial disease diagnosed and followed at the same center between 2005 and 2024 were included. Patients who had other etiologies for axial symptoms, including chronic nonbacterial osteomyelitis, mechanical back pain-overuse injuries, amplified pain/growing pains, and SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) served as the control group. Results: In total, 123 JSpA patients and 74 controls were included in this study. The sensitivity/specificity of the new criteria were 61%/77% with an area under curve value of 0.75 (95% CI: 0.68-0.83) in our cohort. Among different criteria sets, European Spondyloarthropathy Study Group (ESSG) criteria were the most sensitive (sensitivity/specificity 91%/68%), and ASAS peripheral criteria (Assessment of SpondyloArthritis International Society) were the most specific (sensitivity/specificity 67%/84%) in our cohort when compared to ASAS axial criteria (sensitivity/specificity 74%/65%), ILAR (International League of Associations for Rheumatology) (sensitivity/specificity 85%/81%), and ILAR + SI (sacroiliitis) (sensitivity/specificity 67%/74%) criteria. Conclusions: The area under the curve of the new AxJSpA criteria was similar to that of the original report; however, both sensitivity and specificity were lower in our cohort, possibly due to factors like earlier disease presentation and a lower prevalence of chronic structural changes on MRI.

Psoriasis and spondyloarthropathy: consider SAPHO syndrome About a case

SAPHO syndrome is an inflammatory disorder with bone and cutaneous manifestations, for which whole-body bone scintigraphy (WBBS) is frequently used in diagnosis. The WBBS findings of SAPHO syndromes and secondary bone tumors (SBT) have overlapping features, posing diagnostic challenges. In this multicenter study, we aim to identify different bone and joint involvement patterns between the two disease entities through multiple methods to build machine-learning models and explore interpretable variables. The study included 1,193 patients, of which 593 were diagnosed with SAPHO syndrome and 600 with SBT. LASSO regression, logistic regression, and random forest techniques were applied in the training set to identify significant risk factors. Manual management and other methods were evaluated in the validation set to identify the top-performing model and the most interpretable terms. The study developed a model using 15 manually selected terms and multiple machine learning techniques, which demonstrated high diagnostic accuracy in the G1 dataset for (training AUC 0.934, testing AUC 0.929, accuracy = 88.3%, precision = 88.7%, Recall = 88.3%, F1 score = 0.882). The model was compared with logistic regression and random forest models and showed consistent results in the G2 dataset for external validation (AUC 0.957, Youden index = 0.806, sensitivity = 0.820, specificity = 0.986). The pelvis, femur, and ribs (excluding anterior ribs 1st–5th) and thoracic vertebrae 1st–8th were significant predictors of SBT, whereas the sacroiliac joints, sternum, foot, anterior ribs 1st–5th, and clavicle were indicative of SAPHO. This study assesses the effectiveness of WBBS terms in identifying SBT from SAPHO syndrome and utilizes machine learning to help screen features for patients. The final model demonstrates its dependability, providing a valuable tool for accurate and timely diagnosis.